甲磺酸伊马替尼中甲基哌嗪和肼杂质的测定研究

发布时间：2018-06-17 05:09

本文选题：甲磺酸伊马替尼 + 甲基哌嗪　；参考：《浙江工业大学》2017年硕士论文

【摘要】：甲基哌嗪和肼在合成抗癌药物甲磺酸伊马替尼(MIM)过程中,均属于关键物料,物料的引入、迁移、去除,需要阐述清楚。建立高灵敏度的测定方法对于工艺研究、杂质控制、质量标准制订等具有十分重要的意义。固相萃取(SPE)预处理伊马酸(MIM60)后用气相色谱色谱法(GC)测定甲基哌嗪的含量,苯甲醛衍生肼后用高效液相色谱(HPLC)测定甲磺酸伊马替尼及其中间体伊马胺(MIM50)中肼的含量,使两个色谱测定分析方法的灵敏度、准确度和精密度进一步提高。结果表明,固相萃取气相色谱法测定伊马酸中甲基哌嗪的含量,其溶液在24小时内稳定,浓度范围在2.49-17.57μg/mL的线性相关系数(r)为1.0000,定量限(QL)为2.49μg/mL,检测限(DL)为0.83μg/mL,浓度在2.50-15.00μg/mL时回收率接近100%,方法精密度考察的相对标准偏差(RSD)为1.3%。分析方法准确稳定可靠,可以有效定量伊马酸中甲基哌嗪的含量,已有批次样品小于检测限。苯甲醛衍生化高效液相色谱法测定伊马胺和甲磺酸伊马替尼中肼的含量,其溶液在24小时内稳定,在甲磺酸伊马替尼测定中,浓度范围在0.023-0.180μg/mL的线性相关系数为0.9995,伊马胺测定中,浓度范围在2.25-18.00μg/mL的线性相关系数为1.0000,定量限为0.023μg/mL,检测限为0.008μg/mL,甲磺酸伊马替尼测定肼的浓度为0.023-0.128μg/mL时回收率接近100%,伊马胺测定肼的浓度为2.25-12.75μg/mL时回收率接近100%,甲磺酸伊马替尼测定肼的方法精密度考察的相对标准偏差为1.5%,伊马胺测定肼的方法精密度的相对标准偏差为0.26%。分析方法准确稳定可靠,可以有效定量伊马胺和甲磺酸伊马替尼中肼的含量,伊马胺已有批次样品最大为0.02%,甲磺酸伊马替尼已有批次小于检测限。
[Abstract]:Both methylpiperazine and hydrazine are the key materials in the process of synthesizing the anticancer drug imatinib mesylate. The introduction, migration and removal of the materials need to be explained clearly. It is very important to establish a high sensitivity method for process research, impurity control and quality standard formulation. The content of methylpiperazine was determined by gas chromatography (GC), and the content of hydrazine in imatinib mesylate and its intermediate imatinib (MIM50) was determined by high performance liquid chromatography (HPLC) after benzaldehyde derivatization of hydrazine. The sensitivity, accuracy and precision of the two chromatographic methods were further improved. The results showed that the content of methylpiperazine in imaric acid was determined by solid phase extraction gas chromatography, and the solution was stable within 24 hours. The linear correlation coefficient (r) of 2.49-17.57 渭 g / mL was 1.00, the quantitative limit was 2.49 渭 g / mL, the detection limit was 0.83 渭 g / mL, and the recovery was close to 100 when the concentration was 2.50-15.00 渭 g / mL. The relative standard deviation (RSDs) of the method was 1.3B. The method is accurate, stable and reliable, and can be used to determine the content of methylpiperazine in imaric acid. The content of hydrazine in imamide and imatinib mesylate was determined by high performance liquid chromatography with benzaldehyde derivatization. The solution of hydrazine was stable within 24 hours. The linear correlation coefficient was 0.9995 in the range of 0.023 ~ 0.180 渭 g / mL for imatinib mesylate, and the linear correlation coefficient was 0.9995 for the determination of imatinib mesylate in the range of 0.023 ~ 0.180 渭 g / mL. In the range of 2.25-18.00 渭 g / mL, the linear correlation coefficient is 1.00000.The limit of determination is 0.023 渭 g / mL, the detection limit is 0.008 渭 g / mL, the recovery of imatinib mesylate is 0.023-0.128 渭 g / mL, the concentration of hydrazine is 2.25-12.75 渭 g / mL, the recovery of imadine is close to 100g / mL, and the limit of detection is 0.008 渭 g / mL. The relative standard deviation of the method for the determination of hydrazine by tinnitine was 1.5 and the RSD of the method for the determination of hydrazine was 0.26. The method is accurate, stable and reliable, and can be used to determine the content of hydrazine in imatinib and imatinib mesylate effectively. The maximum value of imatinib in the batch is 0.02g, and the batch of imatinib mesylate is less than the detection limit.
【学位授予单位】：浙江工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.72;O657.7

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